The Effectiveness and Safety of Exenatide Versus Metformin in Patients with Polycystic Ovary Syndrome: A Meta-Analysis of Randomized Controlled Trials.

Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects women of childbearing age, resulting in reproductive dysfunction, hyperinsulinemia, and obesity. While several drugs are currently approved for use in these patients, their relative effectiveness remains controversial. The purpose of this meta-analysis was to evaluate the reproductive efficacy and safety of exenatide, a glucagon-like peptide-1 receptor agonist, versus metformin, an insulin sensitizer, in the treatment of patients with PCOS. Nine randomized controlled trials (RCTs) were included, comprising 785 PCOS patients, of whom 385 received exenatide and 400 received metformin. Compared with metformin, exenatide was significantly more effective in treating these patients, as demonstrated by increased pregnancy rate (relative risk (RR) = 1.93, 95% confidence interval (CI) 1.28 to 2.92, P = 0.002), greater ovulation rate (RR = 1.41, 95% CI 1.11 to 1.80, P = 0.004), decreased body mass index (mean difference = - 1.72 kg/m2, 95% CI - 2.27 to - 1.18, P = 0.00001), and improved insulin resistance (standard mean difference = - 0.62, 95% CI - 0.91 to - 0.33, P < 0.0001). There was no significant difference in the occurrence of adverse events (gastrointestinal reactions, hypoglycemia, etc.) between the two therapies. However, given the moderate to high quality and possible bias of the included studies, the available evidence is inconclusive. More high-quality studies are needed to assess the effects of exenatide in order to provide stronger evidence for its use in this patient population.

[Blockade of TLR4/NF-κB pathway promotes the inflammation of Acinetobacter baumannii-infected rats].

Objective To explore the effects of TLR4 on Acinetobacter baumannii (A. baumannii) infection in a rat model. Methods Healthy male SD rats were divided into normal control group, TAK-242 treated group, A. baumannii treated group, TAK-242 and A. baumannii combined treatment group. Rats of TAK-242-treated group were prepared by caudal vein injection of TAK-242 (1 mg/kg). A. baumannii were isolated from intensive care unit (ICU) and the freshly grown bacteria (1×108 CFU/mL) were prepared. Each normal or TAK-242-treated rat was inoculated with 50 µL A. baumannii through trachea. The bronchoalveolar lavage fluid (BALF) and blood were collected at 72 hours after inoculation. The histopathology of lung was evaluated by HE staining. TNF-α and IL-6 were detected by ELISA. The level of phosphorylated NF-κBp65 (p-NF-κBp65) in peripheral blood mononuclear cells (PBMCs) was detected by Western blot analysis. Results A. baumannii were eliminated within 72 hours in normal rats, whereas bacteria continued to replicate rapidly in the lungs of TAK-242 A. baumannii treated group. The pulmonary inflammatory was more severe than the normal rats. The levels of TNF-α and IL-6 increased markedly after the infection. However, the levels of TNF-α and IL-6 in the TAK-242 combined with A. baumannii treated group were lower than those in the A. baumannii treated group. The level of p-NF-κBp65 increased significantly in the PBMCs of the normal rats 72 hours after infected with A. baumannii, but increased slightly in the TAK-242 combined with A. baumannii treated group. Conclusion TLR4/NF-κB pathway plays an important role in the process of A. baumannii infection, and TLR4 can be used as a target molecule in the treatment of A. baumannii infection.

[Activation of platelet activating factor receptor by Acinetobacter baumannii results in oxidative stress and apoptosis in human bronchial epithelial cells].

Objective To investigate the effect of platelet activating factor receptor (PAFR) on human bronchial epithelial (HBE) cells infected by Acinetobacter baumannii (A. baumannii). Methods HBE cells were divided into control group, ginkgolide B (GB) group, A. baumannii infected group, A. baumannii infection and inhibitor group. HBE cells were infected with low dose (1×103 CFU/mL), medium dose (1×105 CFU/mL) and high dose (1×107 CFU/mL) A. baumannii separated from clinical samples. The PAFR activity was blocked by the 10 µmol/L GB. The expression of PAFR was detected using Western blotting in HBE cells. The proliferation ability of HBE cells was detected using CCK-8 assay. The oxidative stress level was evaluated by superoxide dismutase (SOD) and malondialdehyde(MDA) kits. Apoptosis of HBE cells was observed by annexin V-FITC-V/PI staining. The phosphorylation level of PAFR and its downstream molecule JAK1/STAT1 in HBE cells were examined by Western blot analysis. Results Compared with the control group, the expression of PAFR increased significantly in A. baumannii infected group. A. baumannii infection could decrease cell vitality, but increase intracellular oxidative stress, apoptosis, and JAK1/STAT1 phosphorylation. Conclusion PAFR is an important mediator molecule for A. baumannii infection in HBE cells, and PAFR/JAK1/STAT1 signaling pathway plays an important role in the pulmonary infection of A. baumannii.

[Establishment of Acinetobacter baumannii-induced pneumonia model in mice].

Objective To establish Acinetobacter baumannii (A. baumannii)-induced pneumonia models in C57BL/6 mice, and study the molecule mechanism of A. baumannii infection. Methods Eighty C57BL/6 mice were divided into normal control group, cyclophosphamide-treated group, A. baumannii infection group, and cyclophosphamide-pretreated A. baumannii infection group. Immunodeficient mice were prepared by injecting cyclophosphamide intraperitoneally. A. baumannii was isolated from intensive care unit (ICU) and fresh bacteria (1×108 CFU/mL) were prepared. Each normal or immunodeficient mouse was inoculated with 50 µL A. baumannii through trachea. The lung, bronchoalveolar lavage fluid (BALF) and blood were collected at 6, 24 and 72 hours after inoculation. The numbers of white blood cells (WBCs) and neutrophils were detected by cell counting. The histopathology of the lung was evaluated by HE staining. Cytokines such as granulocyte macrophage colony-stimulating factor (GM-CSF), interferon γ (IFN-γ), interleukin 1ß (IL-1ß), IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, tumor necrosis factor α (TNF-α) were detected by ELISA. Results A. baumannii was eliminated within 72 hours after infection in normal mice, whereas the bacteria continued to replicate rapidly in the lungs and blood in the immunodeficient mice. The numbers of WBCs and neutrophils were elevated markedly 6 hours post infection, and return to the normal within 72 hours. However, the numbers of WBCs and neutrophils continuously increased in cyclophosphamide-pretreated A. baumannii infection group, and the pulmonary inflammatory was more severe than that in the normal mice. The cytokines of blood increased markedly 6 hours post infection, and then decreased until 72 hours. However, the cytokines continuously increased in cyclophosphamide-pretreated A. baumannii infection group. Conclusion A. baumannii-induced pneumonia models in C57BL/6 mice were established successfully.

[Caspase-1 inhibitor AC-YVAD-CMK blocks IL-1ß secretion of bone marrow-derived macrophages induced by Acinetobacter baumannii].

Objective To explore the effect of caspase-1 selective inhibitor AC-YVAD-CMK on IL-1ß secretion of bone marrow-derived macrophages (BMDMs) induced by Acinetobacter baumannii (A. baumannii). Methods Macrophages were separated from C57BL/6 mice which were stimulated using different concentrations of A. baumannii. The level of IL-1ß in the culture supernatant was detected by ELISA. The expression of pro-IL-1ß mRNA and protein were detected using the real-time quantitative PCR and Western blot analysis, respectively. The role of caspase-1 in the secretion of IL-1ß was tested by AC-YVAD-CMK treatment to block caspase-1. Pneumonia models in C57BL/6 mice were prepared by A. baumannii inoculation. The level of IL-1ß in bronchoalveolar lavage fluid (BALF) and the morphology of lung were detected by ELISA or HE staining, respectively. Results IL-1ß level in the culture supernatant was up-reregulated by A. baumannii stimulation in a dose-dependent manner. The expression of pro-IL-1ß mRNA and protein were not significantly changed with A. baumannii stimulation. Mature IL-1ß secretion was blocked by AC-YVAD-CMK either in vitro or in vivo. The damage of lung induced by A. baumannii infection in mice was ameliorated by AC-YVAD-CMK. Conclusion AC-YVAD-CMK alleviates pulmonary pathological damage by reducing the caspase-1-mediated IL-1ß secretion.